The adaptation of skeletal muscle to endurance exercise involves alterations in protein metabolism which lead to increases in the concentration of specific proteins. In contrast, contractile activity against a load results in alterations in protein metabolism which lead to hypertrophy. The protein metabolic responses to to the two types of activity occur in insulin-deficient diabetic rats as well as normal rats. We propose to determine the basis for the alterations in protein metabolism by measuring in vivo rates of protein synthesis and protein degradation in skeletal muscle of normal and diabetic rats during a program of endurance training. Turnover will be examined in total muscle protgein as well as in specific myofibrillar and sarcoplasmic proteins. Synthesis and degradation will be monitored by continuous infusion of 3H-leucine using the specific radioactivity of leucine from aminoacyltRNA to calculate absolute rates. Our in vivo studies will focus on the response of the gastrocnemius (fast white), soleus (slow red) and epitrochlearis (fast white) muscles to further ask how different muscle types respond. Protein turnover parameters will also be measured in animals following tenotomy to determine the basis of the compensatory hypertrophy. Endurance exercise produces increases in the insulin sensitivity of skeletal muscle. In vitro preparations of soleus and epitrochlearis muscle will be used to study the relationship between alterations in insulin binding and the respone of protein metabolism to insulin. These studies are important to understand the basis for the adaptive response of skeletal muscle to endurance exercise and contractile activity and will provide insight into the mechanism by which physical conditioning improves the function of muscle and alters the sensitivity of the organism to the anabolic influence of insulin.